Keratinized epithelium is the protective layer of the body and parts of the oral cavity. Cells of the fully differentiated layer, the stratum corneum, contain keratin filaments embedded in a matrix. Keratohyalin granules (KHG) have been proposed as the source of the matrix material. In normal keratinization of epidermis and palate, KHGs are present in cells of the s. granulosum, then disappear when these cells become cornified. KHGs are generally absent from parakeratinized or non-keratinized portions of oral epithelium. The recently isolated stratum corneum basic protein (SCBP) may be the interfilamentous matrix material. SCBP aggregates with keratin filaments in vitro to form macrofibrils in which the filaments are highly aligned. Biochemical and immunologic evidence suggests that SCBP is derived from a higher molecular weight precursor protein in KHGs. Our hypothesis is that SCBP is generated in vivo from the KHG precursor by a specific proteinase, and then associates with keratin filaments forming an insoluble macromolecular complex with a stabilized structure, as found in the s. corneum. This hypothesis will be tested by investigating the mechanism of formation of SCBP from its precursor, by characterizing a possible proteinase responsible for this conversion, and by studying the interaction of SCBP and keratin filaments. The significance of this interaction in keratinization of human oral mucosa will be assessed. SCBP will be tested for its ability to form macrofibrils with keratin filaments isolated from human keratinized (palate), parakeratinized (gingiva), and non-keratinized (buccal) oral epithelium. The concentration of SCBP may be correlated with the type of keratinization in normal oral tissue or with the extent of inflammation in gingivitis, a condition in which the extent of keratinization may change. Thus, variation in this keratohyalin-derived protein, SCPB, is a possible biochemical basis for morphologic differences in keratinization in human oral epithelium.